This is a collection of practical tips gathered from this forum over the years, to help us live better with CLL. I’ve added some personal comments, saying how I myself have taken on board some of these suggestions.

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Chronic lymphocytic leukemia (CLL) is the most common form of blood cancer (leukemia) in the Western world, affecting approximately 1.2% of all cancer patients. This type of cancer starts with the lymphocytes (a type of white blood cells) that are produced in the bone marrow. CLL is characterized by the proliferation of abnormal lymphocytes (B cells) that fail to mature and grow out of control. These abnormal cells accumulate in the bone marrow and lymph nodes, taking the place of other healthy cell types and impeding their normal development. Finding the most suitable therapy for each patient poses a challenge due to the clinical and molecular heterogeneity of this disease, with some patients facing slow disease progression, whereas others face rapid progression and require quick medical response.

The cancer drug ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has remarkable efficacy in most patients with CLL. It is becoming the standard of care for most patients requiring treatment due to its clinical efficacy and mostly tolerable side effects. However, it does not cure the disease, and patients must undergo prolonged periods of treatment. Christoph Bock and his group at CeMM investigated the molecular program with which CLL cells and other immune cells response to ibrutinib treatment in patients with CLL. Their goal was to learn the epigenetic and transcriptional patterns that predict how swiftly the treatment is having an effect on the CLL cells and how long it takes for the disease to respond in each individual patient.

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In a phase 3 trial, acalabrutinib, a second-generation Bruton’s tyrosine kinase (BTK), provided a progression-free survival (PFS) advantage over a chemotherapy-containing standard in frontline treatment of chronic lymphocytic leukemia (CLL).

In the three-arm study, called ELEVATE TN, acalabrutinib (Calquence, AstraZeneca) alone and in combination with obinutuzumab (Gazyva, Genentech) was found to be significantly more effective than chlorambucil plus obinutuzumab for the primary PFS end point, reported investigator Jeff P. Sharman, MD,  at the 2019 annual meeting of the American Society of Hematology (ASH, abstract 31). Dr. Sharman, the director of research at Willamette Valley Cancer Institute, in Eugene, Ore also noted that a trend toward an overall survival (OS) benefit appeared to be emerging for the acalabrutinib combination.

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• A new diagnosis can be a scary, and lonely, time.
• Online communities like CLLANZ, HealthUnlocked, and Patient Power are helping people come together, and cope with complex chronic illnesses such as CLL.
• The patients’ shared experiences and knowledge of their condition, hospitals, healthcare services and drugs is leading to improvements in patient care, both by themselves, and by their carers, and their doctors.
• Knowledgeable patients become their own advocates and ask questions of their doctor, forming a partnership approach.

• Most common adult leukaemia
• Most patients are older than 65
• Cancer of the immune system affecting B-cells
• Can present with a weak immune system
• Each patient’s CLL is different
• Most patients will, often initially, not require treatment. Watch and wait (and worry)
• Most new therapies have improved the prognosis of CLL, but it still remains a chronic condition that can only rarely be cured

• All patients at diagnosis

-Flow cytometry (via blood and / or bone marrow) to confirm CLL diagnosis

• Informative for prognosis and / or therapy determination

-Del17p, and del11q.  These portend for more aggressive disease

-Mutated / unmutated VH gene status assessment (not yet available in New Zealand).

-No CT scan unless symptoms are present:  PET scan can be helpful if Richter’s suspected

• Bone marrow biopsy and aspirate not necessary in absence of cytopenias

The combination of two targeted therapies — ibrutinib (Imbruvika, Pharmacyclics/Janssen) and venetoclax (Venclexta, AbbVie) – has shown impressive results in the front-line treatment of chronic lymphocytic leukemia (CLL).

To read the full story visit Medscape

This article was originally published on Healio

In this Guest Commentary, Ryan W. Jacobs, MD, principal investigator of clinical trials for chronic lymphocytic leukemia at Atrium Health’s Levine Cancer Institute, reviews studies on CLL that will be presented at the ASH Annual Meeting and Exposition. The most anticipated trials will reveal new information on BTK plus BCL-2 inhibition, updates on major clinical trials — including the CLL14 and MURANO trials — early data on CAR T-cell therapy, and more.

There are a lot of studies updating us on new treatment options for CLL, which is not surprising given how rapidly the field has been progressing. Essentially all the major newer drugs being used to treat CLL have some significant updates. There is also a lot to be excited about regarding where the field may be progressing to in terms of chemotherapy-free small molecule inhibitor combinations that are administered over a defined timeline, produce deep remissions and are well tolerated. This will be a review of the notable oral presentations in CLL.

BTK plus BCL-2 inhibition

There has been evidence and recognition for a while now that using both BTK and BCL-2 inhibition together makes sense in terms of complimentary mechanisms of action, the potential to reduce possible mechanisms of resistance, and how well these drugs treat disease in different sanctuaries of the body. For example, ibrutinib (Imbruvica; Pharmacyclics, Janssen), a BTK inhibitor, targets disease well in the enlarged lymph nodes and spleen. Venetoclax (Venclexta; AbbVie, Genentech) is really good at clearing out the circulating disease quite rapidly.

There are five noteworthy oral presentations evaluating the combination of BCL-2 inhibition and BTK inhibition. The most significant in terms of the number of patients on the trial and the length of follow up is the phase 2 CAPTIVATE study (Tam CS, et al. Abstract 35), which looked at the combination of ibrutinib plus venetoclax for 1 year after a 3-month lead-in with ibrutinib (I acknowledge I may be biased as I am a contributing author). The study enrolled 164 patients aged younger than 70 years, which is more than double the number of patients compared with the other oral presentations that are investigating this combination. CAPTIVATE is also unique in that it is not restricted to high-risk patients, which one of the other trials specifically focuses on. This trial looked at MRD negativity in both the peripheral blood and the bone marrow at the end of 1-year combined therapy. That is the information that is going to be reported because the median follow up is only 14.7 months so far, which is not long enough to fully analyze PFS data. The combination seems to be very effective — close to a 100% overall response rate. At the 1-year mark of combined therapy, the highest reported rates of bone marrow MRD negativity was 71%. The concordance rate between MRD negativity and peripheral blood was very high at 93%. This means that most of the patients who were MRD negative in the blood were also MRD negative in the bone marrow.

Read more from the study here